2-Amino-3-(4-bromobenzoyl)phenylacetic acid (generic name: bromfenac) is a compound represented by the following formula (I) and is an acidic non-steroidal anti-inflammatory agent.

2-Amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof is effective for inflammatory diseases of the external segment and the anterior segment of the eyes (for example, uveitis, blepharitis, conjunctivitis, scleritis, and postoperative inflammation, etc.). Particularly, efficacy of such compound for treating uveitis is comparable with steroidal anti-inflammatory agents which have been conventionally used therefor (JP-2-124817-A (U.S. Pat. No. 2,683,676)). 2-Amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof has been put into practical use in the form of an eye drop as sodium salt and 3/2 hydrate in the field of ophthalmology.
Meanwhile, an eye drop having an improved intraocular penetration and intraocular retention of medicaments has been desired in the field of ophthalmology. However, improvement of intraocular penetration and intraocular retention, etc. has not been previously reported on 2-amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof.
With respect to administration to the eyes, examples of medicaments having improvement in absorption promotion into an ocular tissue or intraocular retention include, for example, the followings: H. Sasaki et al., Pharmaceutical Research, 1995, vol. 2, no. 8, p. 1146-1150, discloses that corneal permeability of β-blockers such as atenolol, carteolol, tilisolol, and timolol was accelerated by capric acid in an in vitro experiment; WO 99/22715 discloses that a C3-C7 fatty acid prolonged a retention time of β-blocker in the ocular tissue; and JP-A-63-301822 (U.S. Pat. No. 2,563,336) discloses that a combination of caproic acid, caprylic acid, and capric acid improved corneal permeability of bunazosin hydrochloride which is an α1 adrenergic receptor blocker. In addition, it is also reported that benzalkonium chloride used as antiseptic in an eye drop promotes not only corneal permeability of tilisolol and FITC (fluorescein isothiocyanate)-dextran but also conjunctival permeability thereof slightly in H. Sasaki et al., Journal of Pharmacy and Pharmacology, 1995, vol. 47, no. 9, p. 703-707).
However, in these prior literatures, there is no descriptions with respect to a method for promoting the penetration of 2-amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof into the ocular tissue, and for retaining an effective concentration of 2-amino-3-(4-bromobenzoyl)phenylacetic acid in the anterior aqueous humor for treating inflammatory diseases.
Meanwhile, an organic amine such as trometamol and the like is used as a buffer in the field of ophthalmology. In addition, the organic amine such as trometamol and the like is used for stabilization, solubilization, reduction of irritation, and improvement of antiseptic effect in an eye drop. For example, there is disclosed a method for inhibiting irritation of the eye due to pranoprofen by combination of an eye drop containing pranoprofen with tromethamine or 4-(2-hydroxyethyl)-1-(2-sulfoethyl)piperazine (see JP-A-8-291065 (U.S. Pat. No. 3,170,619)). Further, there is disclosed a method for improving antiseptic effect of sulfa drugs solubilization and by combination of an eye drop containing a sulfa drug with an alkanolamine such as monoethanolamine, diethanolamine, and triethanolamine, followed by dissolution (see JP-B-1-29170; JP-A-59-89616; JP-A-61-12617). There is also disclosed a diclofenac sodium eye drop combined with trometamol or its homolog of not more than 10 carbon atoms as antiseptic and stabilizer (see JP-A-62-242617; JP-A-62-242618).
However, in these prior literatures, there is no description indicating that intraocular penetration of 2-amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof was promoted, and an effective concentration of 2-amino-3-(4-bromobenzoyl)phenylacetic acid was retained in the anterior aqueous humor for treating inflammatory diseases.